This invention relates to the treatment of cystic fibrosis.
Patients with cystic fibrosis suffer from chronic lung problems and digestive disorders. The lungs of cystic fibrosis patients become covered with a sticky mucus which is hard to remove and promotes infection by bacteria. Many CF patients require frequent hospitalizations and continuous use of antibiotics, enzyme supplements, and other medications. The life expectancy of these patients used to be is just under 30 years but appears to be increasing to an extent. There are approximately 40,000 people in the United States with cystic fibrosis.
For many years the causes of cystic fibrosis were a mystery. Today, recent advances in biology have made the cause more clear: cystic fibrosis is caused by an inherited genetic defect. Humans have a gene encoded in their DNA that manufactures a special protein called CFTR. This protein controls the transport of chloride ions across the cell membrane. Each gene is made up of two alleles, a single correctly encoded allele is adequate for normal CFTR production. Thus it is only when a person has two defective CFTR alleles that they actually have cystic fibrosis. Those with a single defective allele are called carriers, and those with two defective alleles have cystic fibrosis. About one in every 23 people in the United States carry at least one defective CFTR gene, which makes it the most common genetic defect of its severity in the United States.
To date, the treatments for cystic fibrosis have not treated early events associated with the progression of the disease.
This invention represents a novel therapy for treating cystic fibrosis patients without the substantial side effects of prior pharmaceutical approaches. Specifically, this invention involves the administration of an inhibitor of phosphodiesterase 2 (xe2x80x9cPDE2xe2x80x9d) that also preferably inhibits phosphodiesterase 5 (xe2x80x9cPDE5xe2x80x9d) to a mammal in need of treatment for cystic fibrosis. In narrower aspects of this invention, this invention involves the administration of compounds of Formula I below to a mammal in need of treatment for cystic fibrosis.
Such novel therapies, we believe, treat the disease by inducing apoptosis in pulmonary macrophages, a feature of cystic fibrosis, that generate lung-damaging metabolites and leukotriene B4.